Hatsue Ogawara

High Th1/Th2 ratio in patients with chronic idiopathic thrombocytopenic purpura.

Abstract:  Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by increased platelet clearance because of antiplatelet antibodies. It was recently reported that the balance of T helper 1 (Th1) and T helper 2 (Th2) subsets has been implicated in the regulation of many immune responses. In this study, the intracellular interleukin‐4 and interferon‐γ production in CD4+ T‐lymphocytes activated by phorbol 12‐myristate 13‐acetate and ionomycin was assessed via flow cytometry in order to determine the clinical significance of the Th1/Th2 ratio in 42 patients with ITP. The study cohort included 28 untreated patients, seven postprednisolone therapy patients and seven postsplenectomy patients. The mean level of the Th1/Th2 ratio in the untreated group was 36.9 (95% CI 25.8–47.9), and significantly higher than in the control group (mean 12.8, 95% CI 9.5–16.1). The mean levels of the Th1/Th2 ratio in the postprednisolone therapy and postsplenectomy groups were 20.5 (95% CI 8.4–32.6) and 16.4 (95% CI 3.1–29.7), respectively, but were no significant differences as compared with control subjects. When untreated patients were divided into two subgroups by Th1/Th2 ratio, the mean level of platelet associated IgG in the high Th1/Th2 subgroup (higher than upper limit of control group) tended to be higher than in the normal Th1/Th2 subgroup. In conclusion, the high Th1/Th2 ratio was closely related to the etiology and disease status of chronic ITP.

Changes in attitudes toward interprofessional health care teams and education in the first- and third-year undergraduate students

The interprofessional education (IPE) program at Gunma University, Maebashi, Japan, implements a lecture style for the first-year students and a training style for the third-year students. Changes in the scores of modified Attitudes Toward Health Care Teams Scale (ATHCTS) and those of modified Readiness of health care students for Interprofessional Learning Scale (RIPLS) at the beginning and the end of the term were evaluated in the 2008 academic year. Two hundred and eighty-five respondents of a possible 364 completed the survey. In both the scales, the overall mean scores declined significantly after the lecture-style learning in the first-year students, while the scores improved significantly after the training-style learning in the third-year students. Exploratory factor analysis revealed that the modified ATHCTS was composed of three subscales, and the modified RIPLS two subscales. Analyses using regression factor scores revealed that the scores of “quality of care delivery” subscale in the modified ATHCTS and those of “expertise” subscale in the modified RIPLS declined significantly in the first-year students. Consequently, IPE programs may be introduced early in the undergraduate curriculum to prevent stereotyped perceptions for IPE, and comprehensive IPE curricula may result in profound changes in attitudes among participating students.

Th1/Th2 Cells in Patients with Multiple Myeloma

Abstract Multiple myeloma (MM) is a lymphoproliferative disorder that is characterized by a proliferation of clonal B cells in various stages of maturation that then infiltrate the bone marrow. MM has been reported to accompany various T cell abnormalities including quantitative and functional defects of CD4+ and CD8+ T cells. Recently, immunotherapy such as dendritic cell therapy, vaccination therapy, and anti-tumor antibody therapy, has been attempted in patients with MM. To develop more effective immunotherapy for patients with MM, further studies are required to identify the immunological abnormalities, especially in T cells, associated with MM. The T helper 1 (Th1) and T helper 2 (Th2) cells are characterized by distinct cytokine production patterns. The Th1 cells produce interferon γ and interleukin-2 (IL-2), and are involved in cell-mediated immunity. The Th2 cells produce IL-4 and promote humoral immunity by stimulating antibody production, particularly IgE responses. Furthermore, Th1 and Th2 cells have been found to cross-regulate each others development. The Th1/Th2 combination has an important role in immune response to many disorders including infection, autoimmune diseases, and malignancies. In this review, we report a Th1/Th2 imbalance in cases of MM, and discuss the relationship between T cell abnormalities and the pathology of MM.

Interleukin-17F gene polymorphism in patients with chronic immune thrombocytopenia

Introduction:  IL‐17F is a novel inflammatory cytokine and plays an important role in some autoimmune diseases. We investigated the association between chronic ITP and the frequency of the single‐nucleotide polymorphism rs763780 (7488T/C), which causes a His‐to‐Arg substitution at amino acid 161.

Clinical significance of regulatory T cells in patients with myelodysplastic syndrome

Objective:  Foxp3+ regulatory T cells (Tregs) play a central role in maintaining immune tolerance. Their expansion in malignant diseases leads to the suppression of host anti‐tumour responses. In this study, we evaluated the clinical significance of Tregs in patients with myelodysplastic syndrome (MDS).

Attitudes toward interprofessional healthcare teams: A comparison between undergraduate students and alumni

The goal of effective interprofessional education (IPE) is high-quality patient-care delivery and attaining a high level of patient satisfaction in clinical settings. We aimed to examine if alumni who have studied in an IPE program at a pre-licensure stage maintain a positive attitude toward collaborative practice (CP) in the postgraduate clinical experience. This paper presents a cross-sectional descriptive study which employed the modified attitudes toward health care teams scale (ATHCTS) to examine the relationship between exposure to clinical practice and the attitudes toward interprofessional healthcare teams. Results indicated that the overall mean score of alumni was significantly lower than that of undergraduate students on the modified ATHCTS. Only “team efficacy” had a significantly lower regression factor score in alumni than undergraduate students. Our findings suggest that changes in professional identity in a team may be due to contact with patients after graduation in the postgraduate clinical healthcare experience. The reduction of attitudes toward healthcare teams in the postgraduate clinical experience may be related to “team efficacy”. We emphasize the need for in-service IPE for sustaining attitudes and providing a useful CP, which results in good clinical outcome.

Interleukin-10 gene polymorphism reflects the severity of chronic immune thrombocytopenia in Japanese patients

Introduction:  T‐helper cell type 1 (Th1) polarization of the immune response has been documented in patients with chronic immune thrombocytopenia (ITP). Interleukin (IL)‐10 is the most important factor regulating Th1 and T‐helper type 2 cytokine synthesis. This study evaluated the impact of IL‐10 polymorphisms on both susceptibility to, and severity of, chronic ITP.

Clinical significance of Th1/Th2 ratio in patients with myelodysplastic syndrome.

In this study, we attempted to evaluate the clinical significance of T helper 1 (Th1)/T helper 2 (Th2) ratio in patients with myelodysplastic syndrome (MDS), five refractory anaemia (RA), four refractory anaemia with ringed sideroblasts (RARS), 31 refractory cytopenia with multilineage dysplasia (RCMD), nine refractory anaemia with excess blast‐1 (RAEB‐1) and seven refractory anaemia with excess blast‐2 (RAEB‐2). Intracellular interleukin‐4 (Th2 cytokine) and interferon‐γ (Th1 cytokine) production was assessed in CD4+ T lymphocytes activated by phorbol 12‐myristate 13‐acetate and ionomycin using flow cytometry. Mean Th1/Th2 ratios in each MDS group were as follows: RA/RARS, 8.8 (95% CI, 5.8–11.8), RCMD, 14.7 (95% CI, 9.5–19.9), RAEB‐1, 10.6 (95% CI, 4.6–16.6), RAEB‐2, 12.8 (95% CI, 3.0–22.7) and control 12.8 (95% CI, 9.6–16.1). There were no significant differences in Th1/Th2 ratio in the RA/RARS, RCMD, RAEB‐1 and RAEB‐2 subgroups when compared to controls. Because Th1/Th2 ratio in the RCMD group was widely distributed, we divided RCMD patients according to Th1/Th2 ratio into three groups (low, normal and high Th1/Th2 groups). There were no differences in severity of cytopenia among the three above groups. However, the percentage of CD8 cells in the low Th1/Th2 group was significantly lower than those in the high group (P < 0.01). These data suggest that Th1/Th2 imbalance induces CD4/CD8 imbalance, and serves as a marker of the biological interplay in immune regulation.

Clinical significance of neutrophil apoptosis in peripheral blood of patients with type 2 diabetes mellitus.

UNLABELLED Although neutrophils are essential components of the natural immune system, they have also been implicated in the pathogenesis of tissue injuries. We assessed the clinical significance of neutrophil apoptosis in the peripheral blood of patients with type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS The study included 52 patients with T2DM (30 men, 22 women). Control subjects were 16 healthy volunteers without diabetes (7 men, 9 women). Neutrophil apoptosis levels were measured active caspase-3 positive rate by flow cytometry. RESULTS The mean rate of neutrophil apoptosis in patients with T2DM was 15.0% (95% confidence interval [CI]: 9.5% approximately 20.5%), while that in the control group was 5.8% (95% CI: 1.6% approximately 10.0%). There were significant negative correlations between neutrophil apoptosis rate and hemoglobin (Hb) A1c levels (r = -0.352, P < .01). The mean rate of neutrophil apoptosis in the patient group with the 3 major complications (diabetic retinopathy, nephropathy, and neuropathy) was 11.1% (95% CI: 5.5%-16.7%, n = 36) and that of another group without complications was 23.8% (95% CI: 11.4%-36.2%, n = 16). There was a significant difference between these 2 groups (P < .05). CONCLUSIONS The neutrophil apoptosis rate in patients with T2DM was significantly correlated with HbA1C levels. The mean rate of neutrophil apoptosis in the patient group with 3 major diabetic complications remained lower than that in another patient group without complications. The inhibition of neutrophil apoptosis by chronic hyperglycemia is thought to promote tissue injury and to enhance the risk of microangiopathy.

Clinical Significance of Peripheral Blood T Lymphocyte Subsets in Helicobacter pylori-Infected Patients

Background. Helicobacter pylori chronically colonizes gastric/duodenal mucosa and induces gastroduodenal disease and vigorous humoral and cellular immune responses. Methods. In order to clarify the immunological changes induced by this infection, we determined the percentage and, as indicated, ratios of the following cells in peripheral blood of 45 H. pylori-infected patients and 21 control subjects: CD4+ T cell, CD8+ T cells, T helper 1 cells (Th1), T helper 2 cells (Th2), CD4+CD25+ T cells, Foxp3+ regulatory T cells (Tregs), CD4/CD8 ratio, and Th1/Th2 ratio. Results. The percentage of CD8+ T cells was significantly lower in H. pylori-infected patients (mean ± SD; 18.0 ± 7.1%) compared to control subjects (mean ± SD; 23.2 ± 7.8%) (P < 0.05). The CD4/CD8 ratio was significantly higher in H. pylori-infected patients (mean ± SD; 3.1 ± 2.4) compared to control subjects (mean ± SD; 2.1 ± 1.0) (P < 0.05). The Th1/Th2 ratio was significantly lower in H. pylori-infected patients (mean ± SD; 10.0 ± 8.5) compared to control subjects (mean ± SD; 14.5 ± 9.0) (P < 0.05). The percentage of CD4+CD25+ T cells in H. pylori-infected patients (mean ± SD; 13.2 ± 6.2%) was significantly higher than that in control subjects (mean ± SD; 9.8 ± 3.4%) (P < 0.05). However, there was no significant difference in Tregs. Conclusion. Tregs did not decrease, but the activation of humoral immunity and Th2 polarization were observed in the peripheral blood of H. pylori-infected patients. In some cases, these changes may induce systemic autoimmune diseases.